DNA甲基化
小RNA
表观遗传学
生物
癌症研究
甲基化
脱甲基剂
癌变
分子生物学
癌症
基因表达
基因
遗传学
作者
Vinay Koshy Varghese,Vaibhav Shukla,Padacherri Vethil Jishnu,Shama Prasada Kabekkodu,Deeksha Pandey,Krishna Sharan,Kapaettu Satyamoorthy
出处
期刊:Life Sciences
[Elsevier]
日期:2019-09-01
卷期号:232: 116668-116668
被引量:8
标识
DOI:10.1016/j.lfs.2019.116668
摘要
Gene regulatory mechanisms determine the multistep carcinogenesis process. Two aspects of epigenetics are microRNA (miRNAs) and DNA methylation that regulate distinct biological mechanisms such as metastasis, apoptosis cell proliferation and induction of senescence. Although critical, the interplay between these two epigenetic mechanisms is yet to be completely understood, particularly in cervical cancer. To study the DNA methylation regulation of miRNAs and its potential role in cervical cancer, we investigated the differential methylation pattern of two candidate miRNAs (miR-375 and miR-196a-1) during cervical cancer progression against normal cervical epithelium (NCE) by bisulfite DNA sequencing. miR-375 and miR-196a-1 were hypermethylated in Squamous Cell Carcinoma (SCC) against NCE and Cervical Intra-Epithelial Neoplasia (CIN) (p < 0.05). Treatment with demethylating agent reactivated the miR-375 and miR-196a-1 expression in SiHa, HeLa and CaSki cells. In vitro artificial methylation by M.SssI followed by dual luciferase assay confirmed miR-375 and miR-196a-1 as methylation regulated miRNAs (P < 0.05). miR-375 and miR-196a-1 expression levels were negatively correlated with methylation levels in clinical specimens. We further identified Replication Factor C Subunit 3 (RFC3) and High Mobility Group AT-Hook 1 (HMGA1) as targets of miR-375 and miR-196a-1 respectively by dual luciferase reporter assay. Our analysis indicates that miR-375 and miR-196a-1 are DNA methylation regulated miRNAs whose deregulation may facilitate pathophysiology of cervical cancer.
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